This is a case of HCC who had been treated with only integrative medicines without receiving surgical treatment or TACE. At the time of the report, the patient's overall survival (OS) was 4 years and 7 months after being diagnosed with HCC. Nevertheless, according to a clinical trial with 2887 patients from China, the median survival was only 9 months (95% CI 11.0–13.0). Furthermore, the OS was only 19.5% at five years. With surgical treatment, median survival was 20.5 months and OS at five years was 42.9%. With TACE, median survival was 7 months and OS at five years was 7.6%. With only conservative treatment, median survival was 2 months and OS at five years 5.1% [11].
During the treatment period, the patient achieved progression-free survival of 4 years and 7 months with reducing AFP levels and remained clinically stable. After 6 months of treatment, AFP levels reached normal and HBV DNA undetected. Over 1 year of treatment (i.e., 20 months after the initial diagnosis of HCC), the CT scan showed no HCC nodules. The herbal supplements used in our case were found to have anti-tumour activity for HCC.
Silymarin, a flavonolignan, is extracted from milk thistle (Silybum marianum). It has been used as a hepatoprotective agent with antioxidant, anti-inflammatory and anticarcinogenic effects. According to a systematic review, in vitro and in vivo studies indicate that silymarin may be a promising option in HCC [12]. Silymarin inhibits the telomerase activity of human HCC cell line HepG2. Telomerase activation is one of the initial steps in hepatocarcinogenesis [13]. Silymarin was also reported to inhibit the proliferation and induce apoptosis in human HCC cell line HepG2 [14]. In vivo studies showed that silymarin could suppress the N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats by modulating the antioxidant defence status of those animals [15]. Also, silymarin administration can decrease cell proliferation, increase apoptosis, and activate the detoxification system in NDEA-induced HCC in rats [16]. Silibinin, a major active constituent of silymarin, was found to inhibit the growth in two different HCC cell lines (HepG2 and Hep3B), exert cytotoxicity, induce apoptosis, and cause cell cycle arrest [17]. The Notch signalling pathway plays a crucial role in hepatocarcinogenesis, and silybin is found to be a potent inhibitor of HCC cell growth by targeting the Notch signalling pathway [18]. A recent research study indicates that Silybum marianum total extract, silymarin and silibinin exert anti-HCC effects through multitple pathways. They improved liver function biomarkers and tumour markers (AFP, CEA and CA 19.9), reduced hepatic production of lipid peroxides, increased hepatic glutathione content and induced the activities of hepatic antioxidant enzymes [19].
Matricaria chamomilla (chamomile) is a well-documented medicinal herb with anti-inflammatory, antioxidant and antitumour activities and is commonly used to treat diverse ailments [20]. Recently, recognition of apigenin, a flavonoid compound in chamomile, as a cancer chemopreventive agent has increased [21]. Research studies have reported that apigenin can inhibit the growth and proliferation of HCC cells, induce cell differentiation and apoptosis, inhibit HCC cell invasion and distant metastasis, inhibit angiogenesis, regulate immunity, enhance the sensitivity and reduce the toxicity of chemotherapies [22].
Luteolin, a flavonoid from many plants, shows anti-cancer activity in many cancer cells, including HCC. Luteolin partially induced apoptosis in human liver cancer SMMC-7721 cells via autophagy [23]. It has been well studied that luteolin can induce cell cycle arrest or apoptosis and sensitise apoptotic cell death induced by tumour necrosis factor or tumour necrosis factor-related apoptosis-inducing ligand in various human cancer cells. The efficacy of luteolin as an anti-HCC agent is mediated by intracellular pathways, involving improvement of the alterations in liver functions, the suppression of oxidative stress and modulation of antioxidant defence mechanisms. Thus, luteolin supplementation may help the safe application of cancer treatment in medicine [24].
Resveratrol has been revealed to exert antitumour effects and is a chemopreventive and chemotherapy agent in various human cancer cells and animal models. In vitro study demonstrated that resveratrol inhibited cell viability, proliferation, invasion and migration of HCC cells by inducing autophagy via activating p53 and inhibiting the phosphoinositide 3-kinase/Akt pathway in a time- and dose-dependent manner. Enhancing autophagy can augment the antitumour effects of resveratrol in HCC [25]. In hepatoma cells (Hepa LcLc7), it inhibits hepatic reductase activity, an enzyme which produces hepatic toxicity at a concentration of 21µM. Resveratrol protects primary hepatocytes in culture against oxidative stress damage by increasing the activities of catalase, superoxide dismutase, glutathione peroxidase, NADPH quinone oxidoreductase, and glutathione-S-transferase [26].
Green tea catechins may possess potent anticancer and chemopreventive properties for several malignancies. Epigallocatechin-3-gallate (EGCG), the active catechin found in green tea, induces apoptosis and inhibits tumour progression through its anti-inflammatory and antioxidant properties by modulating different signalling pathways in several types of cancer, including HCC [27]. PI3K/AKT pathway plays a vital role in the development and progression of HCC cells, mainly reflected in the mechanisms of liver cancer cell proliferation, differentiation and apoptosis. ECGC inhibited HCC cell growth by affecting the cell cycle and inducing apoptosis via downregulation of the PI3K/AKT pathway [28]. The results suggest that EGCG has great potential as an inexpensive, bioavailable chemotherapeutic agent for complementary treatment in HCC therapy [29].
Experimental studies demonstrated that lycopene, a carotenoid abundant in red tomatoes, inhibits the growth of various cancer cells in different organs and prevents chemically induced carcinogenesis in animal models [30]. Various mechanisms have indicated the antitumour activity of lycopene against HCC development and progression. Lycopene has been shown to inhibit liver tumour initiation by diverse mechanisms, including suppressing the expression of cytochrome P 450 2E1 enzymes (involved in activating procarcinogens), scavenging oxygen-free radicals or up-regulating the antioxidant defense system. In addition, several studies reported lycopene’s ability to inhibit HCC promotion, progression and proliferation [31]. Because of its multiple tumour-inhibitory activities, lycopene may be an attractive and promising carotenoid potentially contributing to preventing and treating human cancers, including hepatocellular carcinoma [30]. The combined use of above supplements may have a synergistic effect and this may be a factor in succeessful treatment in this patient.