Sinecatechins: A better prospect for treating anogenital warts.

Sir,

Anogenital warts are the skin tumours caused by human papilloma virus (HPV) that may bother both the patients and their partners. Current treatment options are not satisfactory due to low efficacy and high recurrence rates. Although prophylactic vaccines have been recommended for adolescent women, more effective treatment modalities for anogenital warts are still needed.

Topical Sinecatechins Ointment 15% is the first FDA approved botanical drug for treating anogenital warts.[1] Sinecatechins are a standardized extract of green tea leaves from Camellia sinensis, a species of the Theaceae family, containing polyphenols; particularly catechins (more than 85%). It contains eight different catechins and other green tea components. The main catechin in sinecatechins ointment his epigallocatechin gallate (EGCG), which has the highest biological activity.[2]

Catechins exert multiple biologic activities by inhibiting a number of proteins, including enzymes involved in oxidative stress, blocking the kinases needed in tumour cell signalling and induction of apoptosis. These postulated mechanisms presumably contribute to the therapeutic effect of sinecatechins ointment.

The proposed mechanisms of action of sinecatechins are:

Anti-oxidant activity

The direct action of catechins is scavenging the reactive oxygen free radicals. Catechins may exert indirect antioxidant activity via inhibitory effects on transcription factors (e.g., nuclear factor-kB [NF-kB], activator protein-1 [AP-1]) and also inhibits the enzymes with activity that increases oxidative stress (e.g., lipoxygenases, cycloxygenases, and inducible nitric oxide).[3] EGCG also induces expression of endogenous antioxidant systems.

Anti-proliferative activity

HPV E6 (early gene E6) degrades p53 (a tumour suppressor gene), inhibits the pro-apoptotic protein BAK, activates telomerase and stabilizes Src-family kinases. HPV E7 (early gene E7) inactivates Rb (a tumour suppressor gene).

Conventionally, the Rb inhibits cell proliferation by binding to the E2F transcription factor (which controls the G1/S phase checkpoint of the cell cycle). Degradation of Rb by HPV E7 can result in uncontrolled cell division. A normal cell would react to this excessive cell division by p53-dependent apoptosis; but the presence of HPV E6 prevents apoptosis by deactivation of p53 and BAK. The end result of their combined action (E6, E7) is cellular proliferation.[4] Catechins check the proliferation of cells by inhibiting kinases (receptor tyrosine kinases, telomerase) and promoting apoptosis.

Immuno-stimulatory activity

HPV evades the immune system by reducing the expression of viral proteins in the immunogenic lower epithelial layers and decreased production of interferons. Catechins increase the activation of macrophages, lymphocytes, Langerhans cells and induction of cytokines (IL-1β, TNF-α, IFN-γ), thereby eliciting cell-mediated immunity against HPV.

To conclude, not only has the sinecatechins had a wide spectrum of action but also the low recurrence rate (6.5%).[5] Hence, it could be a better option to treat anogenital warts in future.