Acupuncture and Chinese Medicine
Acupuncture is the major form of traditional Chinese medicine (TCM) in American, but in China, the major form is Chinese herbs (Chinese medicine).
Acupuncture is mainly applied to help cancer or treatment related symptoms, on very rare occasions, complete remission was reported in some case reports. The acupuncture technique can also be used to combine other new technology, to form a new therapy. For example, it has been used to combine electrical chemistry treatment, to produce local hydrogen and precisely destroy cancer cells. Chinese herbs has been administered in various situations of cancer care, alone or integrated with conventional medicine.
More and more evidence show that combination of acupuncture and Chinese herbs can have a better clinical outcome.
Acupuncture
The National Cancer Institutes (NCI) generated The Physician Data Query (PDQ®) database, which contains summaries on a wide range of cancer topics, information about cancer-related drugs and drug combinations, cancer-related dictionaries and drug terms, genetics term, and provides a directory of genetics services providers. PDQ is used by the general public and health professionals seeking cancer-related information. For the health professional version of PDQ regarding acupuncture, provides an overview of the use of acupuncture as a treatment for individuals with cancer or cancer-related disorders, please use this link: https://www.cancer.gov/about-cancer/treatment/cam/hp/acupuncture-pdq ; for the patient version, please use this link: https://www.cancer.gov/about-cancer/treatment/cam/patient/acupuncture-pdq.
Symptoms
In America, Acupuncture is commonly used clinically to
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manage cancer-related symptoms
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treat side effects induced by anticancer therapies
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boost blood cell count
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enhance lymphocyte and natural killer (NK) cell activity.
In cancer treatment, its primary use is symptom management; commonly treated symptoms are
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cancer pain
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chemotherapy-induced nausea and vomiting (N/V)
and other symptoms that affect a patient’s quality of life, including
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weight loss
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anxiety
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depression
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cough
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coughing up blood
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speech problems
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insomnia
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poor appetite
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fatigue
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xerostomia
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hot flashes
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chemotherapy-induced peripheral neuropathy
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gastrointestinal symptoms (constipation and diarrhea
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postoperative ileus
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chemotherapy-related cognitive problems
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hiccups
It is noteworthy that almost all reported clinical studies on the effects of acupuncture on cancer or cancer therapy–related symptoms focus on symptom management rather than the disease itself. Investigations into the effects of acupuncture on chemotherapy-induced nausea and vomiting, many of which were randomized and well-controlled, produced the most convincing findings. A number of randomized controlled trials have reported on the effect of acupuncture in alleviating other cancer treatment-associated side effects, with many showing promising evidence supporting the use of acupuncture. Additional phase III clinical trials are ongoing.
In clinical practice, most acupuncturists in the United States use the traditional theories and principles of Chinese medicine. A 2017 survey of 472 licensed acupuncturists in the San Francisco Bay area reported that 77% were caring for patients with cancer, and 44% have training specific to the needs of patients with cancer.
Although the mechanism of acupuncture is not fully understood, it has been proposed that beneficial results are mediated by changes in neurohormones and cytokines. Animal research suggests that acupuncture achieves its anesthetic effect by stimulating nerves in the muscle, which then relay the signal to the spinal cord, midbrain, and hypothalamus-pituitary system, ultimately triggering release of neurotransmitters and hormones, such as endorphins and enkephalins.
Laboratory and animal cancer studies have also explored the mechanisms of acupuncture through the activation and modulation of the immune system. Previous animal and human studies have suggested that acupuncture worked through immunomodulation, with significant changes in cytokines including interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha). These studies were limited by small sample size and occasional conflicting results. Acupuncture has been associated with significant changes in proinflammatory cytokines including IL-1-beta, IL-6, IL-17, and TNF-alpha. In addition, studies showed that acupuncture needle manipulation stimulated surrounding connective tissues and sensory nerves and affected adenosine-mediated peripheral sensory modulation.
Acupuncture can also stimulate expression and secretion of somatostatin, whose analog has been reported to inhibit growth of prostate cancer, colon cancer, breast cancer, GI cancers and lung cancer. Some case reports also showed that acupuncture alone resulted in completer remission of tumor. Thus, acupuncture conjunction treatment is potentially increase life expectance of cancer patients and facilitate reducing tumor size.
Tumor size (Mechanism Research)
A team of Chinese scientists adapted the traditional technique to create a form of “electro-chemotherapy” (similar to electrical acupuncture) to treat laboratory mice with brain tumors, shrinking them to less than 1 percent (see the red rectangle below) of their initial size.
(A) Schematic illustration of C6 tumor xenograft establishment, blank and H2-ECT procedures, and therapeutic outcome (n = 3). (B) Typical photographs of the tumor-bearing mice and tumor lumps, and their control groups, before and after 15 days of first treatment in different conditions (10 min twice a day for first 3 days). Red circle indicates the eliminated tumor in this case. Scale bar: 1.5 cm. (C) The body weights of C6 tumor-bearing nude mice with different groups, recorded every day. (D–F) Tumor weight and tumor volume dissected and relative tumor volume after 15 days of first treatment in different conditions (10 min twice a day for first 3 days, n = 3). All the data are represented as mean ± SEM. n denotes the number of mice. n = 3, P<0.05 and P<0.005 representing statistical significance, which is evaluated by Student’s two-sided t-test with GraphPad Prism software compared to the control group.
Another group of investigators found that acupuncture and/or cyclophosphamide (CTX) both reduced the size of the solid tumors of breast cancer. When used in conjunction, the tumor size reduction was even more obvious. The mechanisms are associated with inhibition of angiogenesis.
Acupuncture treatment was also be observed to delay tumor growth and changes of intestinal bacteria in osteosarcoma tumor-burdened mice.
β-endorphin is one of key components related to acupuncture treatment. The cancer-preventive effect of β-endorphin is mediated through the suppression of sympathetic neuronal function, which results in increased peripheral natural killer cell and macrophage activities, elevated levels of anti-inflammatory cytokines, and reduced levels of inflammatory cytokines. β-endorphin inhibition of tumor progression also involves alteration in the tumor microenvironment, possibly because of suppression of catecholamine and inflammatory cytokine production, which are known to alter DNA repair, cell-matrix attachments, angiogenic process, and epithelial-mesenchymal transition. Thus, β-endorphin cell therapy may offer some therapeutic value in cancer prevention.
β-Endorphin neuronal cells in the hypothalamus control the neoplastic growth and progression of tumor cells, likely by modulating one or more of the factors indicated. Effects include the activation of parasympathetic nervous system control of lymphoid organs, causing activation of innate immune cells (macrophages and NK cells) and an increase in anti-inflammatory cytokine levels in the circulation. The hypothalamus-pituitary-adrenal gland (HPA) axis and subsequent stress hormones released from the adrenal gland and sympathetic nerve terminals (glucocorticoids and catecholamines) may also be suppressed. In a tumor microenvironment, these hormonal and cytokine changes downregulate inflammation-mediated epithelial–mesenchymal transition (EMT) and, thereby, suppress cancer progression. Collectively, these effects create an unfavorable environment for tumor initiation, growth, and progression.
Representative references:
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Qi G, et al. A green, efficient and precise hydrogen therapy of cancer based on in vivo electrochemistry. National Science Review, 2020;7(3): 660–670.
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National Cancer Institutes. Acupuncture (PDQ®)–Health Professional Version. https://www.cancer.gov/about-cancer/treatment/cam/hp/acupuncture-pdq
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Tian Y et al. Acupuncture enhances anticancer effects of cyclophosphamide on 4T1 tumors via suppression of angiogenesis in BALB/c mice. Journal of Traditional Chinese Medical Sciences. 2017;4(2):216-221.
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Sarkar DK et al. Regulation of cancer progression by β-endorphin neuron. Cancer Res. 2012;72(4):836-40.
Chinese Medicine
Cancer treatment with traditional Chinese medicine (TCM) has a long history. Discussions of cancer appeared in classical works, such as The Yellow Emperor’s Inner Canon and The Classic of Medical Problems, more than 2000 years ago. Concepts of diagnosis and treatment, such as strengthening body resistance and eliminating pathogens, treating both the manifestation and root cause, treating the same disease with different methods, and treating different diseases with the same methods, have been proven by clinical practice. These concepts have become characteristics and advantages of TCM for cancer prevention and treatment, as demonstrated by modern technology and methods. Heritage has laid the foundation for the innovation and development of cancer treatment with TCM, attracting more and more international attention and cooperation.
Since 1950s, Chinese scholars have carried out scientific research on the use of TCM for the prevention and treatment of cancer, clarifying the different effects of TCM on cancer in different stages. TCM combined with modern medicinal means could improve symptoms, enhance quality of life, prevent recurrence and metastasis, and prolong patients’ survival.
The efficacy of traditional Chinese medicine (TCM) in cancer treatment.
Supporting role of TCM during radiochemotherapy
Radiotherapy and chemotherapy can damage the qi and blood, essence and fluid, and the function of the five viscera and six bowels. Common symptoms include fatigue, apocleisis, nausea, vomiting, and leucocyte decline. Local side effects include stigmata, loss of hair, mucosal erosion, ulcer, edema and hemorrhage. During radiotherapy and chemotherapy, TCM treatment can reduce toxic side effects, such as: myelosuppression, gastrointestinal reactions, hepatic or renal impairment, and skin and mucosa radiation injuries. TCM can improve the clinical efficacy of radiotherapy and chemotherapy, guided by therapeutic principles of tonifying qi and producing blood, strengthening the spleen and stomach, nourishing the liver and kidney, and removing heat from blood and toxic material from the body. TCM combined with chemotherapy has shown a favorable effect in improving efficacy with less adverse reactions. This has been substantiated by the inclusion of TCM into the 6th–11th Five-Year Plans, as well as in meta-analyses by scholars in China and abroad. For instance, McCulloch et al. analyzed 34 randomized studies representing 2815 patients. Twelve studies (n = 940 patients) reported a reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% confidence interval [CI], 0.52 to 0.87); 30 studies (n = 2472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). McCulloch et al.’s study concluded that Astragalus-based TCM may increase the effectiveness of platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC).
The therapeutic function of TCM in advanced cancer patients
For advanced cancer patients, elderly patients, or in those for whom radiotherapy and chemotherapy are unsuitable, TCM has its advantages. For example, with slight adverse reactions, TCM can stabilize tumor lesions, improve symptoms, enhance the quality of life, and prolong survival time. Liu et al. enrolled 304 patients with stage III-IV adenocarcinoma lung cancer in their study and compared chemotherapy and TCM groups. The DCR of the TCM group was 67.83% versus 48.12% in the chemotherapy group (P < 0.01). Symptoms such as coughing, hemoptysis, chest pain, pyrexia, and anorexia were improved in the patients treated with TCM.
The therapeutic function of TCM in postoperative cancer patients
Traditional Chinese medicine plays a role in the treatment and prevention of cancer recurrence and metastasis and prolongs the survival time of postoperative cancer patients. Liu et al. studied the effect of Yifei Kangliu decoction in 201 patients with stage III-IV NSCLC.The metastasis rate in the TCM combined with chemotherapy group was 13.4% versus 35% in the chemotherapy only group (P < 0.05). Lin and Zhang observed 537 patients with postoperative NSCLC. The recurrence and metastasis rates were 45.1%, 50.3%, and 55.8% in the Shen Yi Capsule, Yifei Qinghua mastic, and control groups, respectively.
Prevention and treatment with TCM in precancerous lesions
In view of preventive treatment before disease onset, TCM applied at an early stage can treat precancerous lesions and reduce the incidence of cancer. In a meta-analysis on esophageal cancer, Chen et al. reported that the incidence rate of the precancerous lesions in the TCM treatment group was lower than that of the control group (d = 0.0613, 95% CI 0.0456–0.0769). Miu et al. evaluated the clinical effect of TCM in precancerous lesions of esophageal cancer. They concluded that TCM could improve atrophy of gastric mucosa and intestinal metaplasia, dysplasia, infection of helicobacter pylori, and the clinical symptoms of patients (RR 1.90, 95% CI 1.60, 2.27).
Furthermore, TCM also plays roles in the perioperative period and rehabilitative stage. In the perioperative period and after surgery, TCM can strengthen a patient’s physique, helping to prevent and treat postoperative complications, facilitate postoperative rehabilitation, and regulate immune functions, such as sputum retention after lung cancer surgery, limb swelling in postoperative breast cancer patients, intestinal adhesion related to abdominal surgery, and bile reflux gastritis after gastric cancer surgery. Under the guidance of TCM theory, integral regulation aimed at mentality, nutrition, and physical fitness could relieve adverse reactions, alleviate dysfunction, and promote physical and psychological recovery.
Achievements of TCM in oncology in the last fifty years
In the last 50 years, clinical research summarizing clinical experience has proven that the use of TCM in cancer therapy has decreased toxicity and enhanced the efficacy of radiochemotherapy, prolonged survival in advanced cancer patients, and assisted in the prevention and treatment of recurrence and metastasis. Today, studies focus upon designing a comprehensive regimen and diagnostic and treatment practices guidelines. In the field of laboratory research, studies of TCM have moved focus from screening antineoplastic Chinese medicine, anti-tumor metastasis, and immune regulation, to the biological and behavioral research of tumor stem cells, intervention in the body’s internal environment, and the tumor microenvironment. The achievements of the last 50 years in developing the theory and scientific connotation of TCM in cancer prevention and treatment have served to clarify the position and function of TCM, and promote international exchange and cooperation.
The mechanism of traditional Chinese medicine (TCM) in cancer treatment.
A Nationwide Matched Cohort Study conducted in Taiwan showed that long term Chinese herb user can prolong the median survival of stomach cancer patient after surgery from 3.5 years to more than 14 years, 4 times longer.
Kaplan–Meier curves of overall survival in patients with gastric cancer after surgery and adjuvant chemotherapy among TCM nonusers, short-term TCM users, and long-term TCM users.
For good long term clinical outcome, we strongly recommend receiving treatment regularly, to have sufficient duration and dosage.
Green Hydrogen Therapy
This modality is good for superficial tumors such as breast cancer, skin cancer and enlarged lymph nodes.
The mechanism
Hydrogen gas (formula: H2) possesses multiple bioactivities, including anti-inflammation, anti-reactive oxygen species, and anti-cancer. Growing evidence has shown that hydrogen gas can either alleviate the side effects caused by conventional chemotherapeutics, or suppress the growth of cancer cells and xenograft tumor, suggesting its broad potent application in clinical therapy.
The scientific report of minimal invasive hydrogen therapy
This in vivo hydrogen H2 generation electrochemotherapy (H2-ECT) of tumors, by combined use of Chinese acupuncture Fe needle electrode and in vivo electrochemistrymarkedly inhibited tumor growth. The modality kills cancer cells by virtue of the acidic microenvironment of the tumor and in vivo electrochemical technology. The acupuncture electrodes inserted in the acidic tumor area and working under the applied voltage of 2.5V-3V, produce effectively sufficient H2 to damage and kill cancer. The method is highly biosafe without an obvious poisoning effect, solving the difficult problems of material metabolism and biotoxicity in conventional therapeutic methods for clinical applications. By taking advantage of the puncture positioning, gas diffusion effect and self-protection mechanism of H2 generation, the H2-ECT method provides strong selectivity and targeting to effectively and precisely kill tumors, with minimal damage to healthy tissues. The effectiveness of the method has been demonstrated by in vivo treatment of glioma and breast cancers of diseased mice. More importantly, as the volume of the tumor tissue determines the total amount of hydrogen ions within the tumor, the larger tumors provide more hydrogen ions to produce enough hydrogen for effective treatment. Consequently, in principle, irrespective of the size of the tumor, the inherent volume effect of the method can solve the defect of insufficient hydrogen generation during the therapy process.
(A) Schematic diagram of green H2-ECT therapy in vivo. (B) Schematic EC processes of two acupuncture Fe electrode systems showing anodic Fe dissolution and cathodic H2 production. (C–E) The H2-production polarization curves of acupuncture electrodes recorded, respectively, in simulated body fluid (SBF, pH = 6.0) under three different voltages (C), in SBF but with different pH (5.5, 6.0, 6.5, 7.0 and 7.5) at 3 V (D), and in fresh pork (mimicking complex tumor tissue) at two pHs (6.0 and 7.4) (E). (F) Dissolved amount of iron from the anode during the EC process. (G) The dependence of H2 production of the system on various pH levels in SBF recorded at 3 V for 10 min (n = 3). (H, I) The dependence of the amounts of dissolved iron and produced H2 on voltages varying from 0 to 3 V, each for 10 min duration, at pH = 6.0 and 7.4, respectively (n = 3). All the data are represented as mean ± SEM (standard error of the mean). n denotes samples or number of experiments. n = 3, P < 0.0001 representing the statistical significance of different pH values (pH = 7.5 and pH = 6.0), which is evaluated by two-tailed Student's t-test with GraphPad Prism software.
(A) Schematic illustration of C6 tumor xenograft establishment, blank and H2-ECT procedures, and therapeutic outcome (n = 3). (B) Typical photographs of the tumor-bearing mice and tumor lumps, and their control groups, before and after 15 days of first treatment in different conditions (10 min twice a day for first 3 days). Red circle indicates the eliminated tumor in this case. Scale bar: 1.5 cm. (C) The body weights of C6 tumor-bearing nude mice with different groups, recorded every day. (D–F) Tumor weight and tumor volume dissected and relative tumor volume after 15 days of first treatment in different conditions (10 min twice a day for first 3 days, n = 3). All the data are represented as mean ± SEM. n denotes the number of mice. n = 3, P < 0.05 and P < 0.005 representing statistical significance, which is evaluated by Student's two-sided t-test with GraphPad Prism software compared to the control group.
Therapy of Anti-Warburg Effect
The Mechanism
In oncology, the Warburg effect is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme".
Cellular respiration is the process by which living organisms decompose organic matter to inorganic matter for producing energy required for survival. Sequentially, this encompasses the glycolysis process, the tricarboxylic acid cycle (TCA cycle, also called Krebs cycle), and the electron transport system. In normal cells, glucose is converted to pyruvate through glycolysis in the cytoplasm, and the pyruvate enters the mitochondria where it is completely degraded. This process requires oxygen, and 38 ATPs are finally produced from one molecule of glucose: 2 ATPs during glycolysis, 2 ATPs in the TCA cycle, and 34 ATPs in the electron transport system. Under hypoxic conditions, the pyruvate is converted to lactic acid, which accumulates instead of entering the TCA cycle. In cancer cells, there is an abnormal progression of metabolism that only utilizes glycolysis. In normal cells, 38 ATPs are generated with one glucose molecule, whereas only 2 ATPs are generated in cancer cells (Figure 1). Consequently, the cancer cells require more glucose molecules than normal cells to obtain enough energy to survive. This is a remarkable characteristic of cancer cells and has recently been applied as a method of detecting cancer by exploiting the characteristic of excessive glucose utilization by cancer cells. It is essential to consider that cancer cells complete the glycolysis process regardless of absence or presence of oxygen. When cancer cells only obtain glycolysis-dependent energy even in the presence of oxygen, the effect is called the “Warburg effect”.
Figure 1. Differences in glycolysis pathways between normal cells and cancer cells. (A) In the presence of oxygen, normal cells produce carbon dioxide up to 38 ATPs per glucose molecule through glycolysis, TCA cycle, and electron transport system. In a hypoxic environment, pyruvates are accumulated without going through the TCA cycle. These accumulated pyruvates in the muscle tissue are converted to lactic acid and only produce 2 ATPs. (B) Cancer cells only use the glycolysis process, regardless of the presence or absence of oxygen; 2 ATPs are produced per glucose molecule and, therefore, compared to normal cells, more glucose is required to obtain energy.
Cancer metabolism Involved in the Warburg effect includes: 1. changes in the tumor microenvironment; 2. changes in the signaling pathways; 3. change from oxidative metabolism to reduced metabolism; 4. consumption of glutamine; 5. lipid biosynthesis and 6. drug resistance.
Aerobic glycolysis is best characterized by a shift of pyruvate carbons away from the TCA cycle and towards fermentation, rather than an upregulation of glycolysis at the expense of oxidative phosphorylation
Chinese medicine and Warburg effect
Formula of Chinese herb is the main form of method in the clinical application of traditional Chinese medicine. Using Shenmai Yin to treat S180 tumor-bearing mice with spleen deficiency, Shenmai Yin can significantly inhibit tumor growth and reduce the total LDH activity of tumor tissue; Shenmai Yin does not affect LDH1 activity, but reduces LDH5 activity, suggesting that it inhibits the reduction of pyruvate into lactic acid.
The water extract of Chinese herb, Bangzhilian, BZLIO1, has selective cytotoxicity to breast cancer cells, which is mainly attributed to the induction of a large amount of reactive oxygen species in breast cancer cells and then DNA damage, and the excessive activation of poly ADP ribose polymerase caused by DNA damage further inhibits the cell glycolysis, manifested as decreased LDH activity and reduced lactic acid production, eventually leading to decreased ATP and cell necrosis.
Regarding the active ingredients of Chinese herbs, it has been found that arctigenin, pulsatilla saponin, tanshinone Ⅱ A, chrysin, matrine, oxymatrine, dioscin A, wogonin, oleanolic acid, shikonin, Arsenic trioxide, resveratrol, phyllophyllin A, apigenin, epigallocatechin gallate and curcumin, etc., either alone or in combination with other drugs, have shown good preliminary effects.
Representative References:
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Kim SH, Baek KH.Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect. Int J Mol Sci. 2021 Jun 8;22(12):6173. doi: 10.3390/ijms22126173.
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Luengo A, Li Z, Gui DY, Sullivan LB, Zagorulya M, Do BT, Ferreira R, Naamati A, Ali A, Lewis CA, Thomas CJ, Spranger S, Matheson NJ, Vander Heiden MG. Increased demand for NAD+ relative to ATP drives aerobic glycolysis. Mol Cell. 2021 Feb 18;81(4):691-707.e6. doi: 10.1016/j.molcel.2020.12.012.
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Coverdale J, Romero-Canelón I, Sanchez-Cano C, Clarkson G, Habtemariam A, Wills M, Sadler P. Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells. Nat Chem. 2018 Mar;10(3):347-354. doi: 10.1038/nchem.2918.
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Soldevila-Barreda JJ, Romero-Canelón I, Habtemariam A, Sadler PJ.Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design. Nat Commun. 2015 Mar 20;6:6582. doi: 10.1038/ncomms7582.
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Fong S, Shoemaker M, Cadaoas J, Lo A, Liao W, Tagliaferri M, Cohen I, Shtivelman E. Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells. Cancer Biol Ther. 2008 Apr;7(4):577-86. doi: 10.4161/cbt.7.4.5535.