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the protective effect of coffee was reliable across different invasion and defeating sister chromatid interactions in human
[38]
subgroups at increased HCC risk. lymphocytes. Toad skin secretion bufalin (Bufotoxin) could
induce apoptosis in human-leukaemia cells modifying the
After the publication of these meta-analyses, other studies expression of some apoptotic genes. Other toad skin
[39]
regarding the protective role of coffee in the HCC setting secretions such as 3-formyloxyresibufogenin, 19-oxobufalin,
have been published. The first one, was a multicentre 19-oxodesacetylcinobufagin, 6-hydroxycinobufagin and
study by Bamia et al. including 201 HCC cases. Authors 1-hydroxybufalin seem to have inhibitory properties on KB,
[30]
demonstrated that coffee intake was associated with a human promyelocytic leukemia cells (HL-60) and MH-60
[31]
decrease of 72% in HCC risk. Setiawan et al. conducted a cancer cell lines. Mylabris phaleratais (Mylabris) can lead to
[40]
large population-based prospective cohort study (451 HCC) the apoptosis of tumor cells while Atractylodes might bring
[41]
showing that drinkers of 2-3 cups/day respect to abstinent apoptosis and have cytotoxic effects against tumor cells.
[42]
subjects, had a 38% of HCC risk reduction. In addiction, Bupleurum falcatum shows a significant anti-cell adhesive
patients drinking 4 or more cups/day had a 41% of risk activity on solid tumor cells and Curcuma longa has a
[43]
drop. Feld et al. again suggested that regular ingestion relevant immunostimulatory activity. [44]
[32]
of coffee in patients with chronic liver disease can make
slower the progression of liver fibrosis, preventing both Concerning the prevention ability of herbal products, a
cirrhosis and HCC. Petrick et al. developed the Liver Japanese herb called Sho-saiko-to has to be cited since it is
[33]
Cancer Pooling Project based on North-American data reported in the Asian-Pacific guidelines. In a randomized
[7]
[45]
and including 1,212,893 patients (with 860 HCC cases). A controlled trial (RCT), Sho-saiko-to was shown to improve
high caffeinated coffee consumption (≥ 4 cups/day) was liver function in patients with chronic hepatitis. Also Oka et
associated with a lower risk of HCC in comparison to a al. reported that Sho-saiko-to may prevent the development
[46]
[34]
lesser intake. In a Japanese cohort-study including 258 of HCC in cirrhotic subjects. Successive studies with liver cell
cases, an inverse association was reported between coffee lines confirmed the above-cited suggestions. [47,48]
and mortality associated to HCC. Interestingly, the hazard
[49]
of HCC-related death for abstinent patients was two-fold In 2013, Zhai et al. compared in a RCT the efficacy of TCM and
higher compared to coffee drinkers, and this was true also TACE in preventing recurrence of small HCC after resection.
for few consumption (≥ 1 cup/day). Authors tested TACE or TCM as adjuvant therapy for patients
who underwent surgery without evidence of recidivism. One
TCM hundred and eighty-eight patients received Cinobufacini
injection (extract from Bufo bufo gargarizans Cantor) and Jiedu
Many authors proposed TCM-based therapy alone or Granule (a compound herbal medicine). The other patients
in combination with standard loco-regional therapies (191 cases) were assigned to the TACE subgroup. TCM was
for prevention or treatment of HCC [Table 1]. The main associated with decreased HCC recurrence after resection in
TCM products include combinations of different herbal comparison to TACE, with similar adverse events.
medicines or animal/insect extracts. Astragalus shows
immunomodulatory properties and anti-tumor activity. Regarding the use of TCM alone as therapeutic tool, Tian
[50]
It seems to reinforce Lymphokine Activated Killer cell et al. demonstrated that it may be effective in subjects
activity restoring the T-cell function suppressed in cancer affected by middle/late stage HCC. In this RCT, 97 patients
patients. [35,36] The Panax Ginseng has inhibitory effects on were treated with Oleum fructus bruceas, Ganji Decoction and
cell proliferation and angiogenesis restraining tumor cell external application of Ailitong, and 48 patients received
[37]
Table 1. The main natural products from Traditional Chinese Medicine
Product Type Main property/ies Studies in humans RCTs Meta-analysis Ref.
Astragalus Herb Restores T-cell Yes Yes Yes [35,36,53,55]
Panax Herb Anti-proliferation and Yes Yes Yes [37,38,55]
Ginseng angiogenesis
Bufotoxin Toad skin secretion Induces apoptosis Yes Yes Yes [39,55]
Atractylodes Herb Induces apoptosis No No No [42]
Bubleurum falcatum Herb Anti-adhesive activity No No No [43]
Curcuma longa Herb Immunostimulatory No No No [44]
activity
Cinobufacini Bufo skin estract Induces apoptosis Yes Yes No [49]
Jiedu Herb Unreported Yes Yes No [49]
Sho-saiko-to* Herb Decreases collagene Yes Yes No [7,45-48]
type 1
Bruceas Fruit estract Unreported Yes Yes No [50]
Ganji Herb Unreported Yes Yes No [50]
Ailitong Herb Unreported Yes Yes No [50]
Kanglaite Herb Immunomodulation Yes Yes Yes [56]
*It comes from the Japanese Tradition

Hepatoma Research | Volume 2 | March 9, 2016 73