BmKn-2 Scorpion Venom Peptide for Killing Oral Cancer Cells by Apoptosis

Abstract

Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an IC 50 value of 29 µg/ml. The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells.

Scorpion and spider venoms in cancer treatment: state of the art, challenges, and perspectives

“…Some scorpion venoms target caspases, mitochondria, Bcl-2, and BAX and may thereby contribute to cancer treatment. BmKn-2 peptide (29 µg/ml) from BmK venom killed cultured human oral squamous carcinoma (HSC-4) cells through the induction of apoptosis, as reflected by increased activated caspase-3, -7 and -9 mRNA levels [27]. BmKn-2 also induced apoptosis in HSC-4 and human mouth epidermoid carcinoma (KB) cells by activating P53 and increasing BAX/BAX and decreasing BCL-2/BCL-2 expression of both transcripts and proteins.…”

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

“…Tong‐ngam, Roytrakul, and Sritanaudomchai (2015) determined the anticancer attribute of B. martensii Karsch venom against an oral cancer cell line with a mortality rate of 95% within 24 h. Li, Hu, Zhang, and Wei (2006) revealed a tumoricidal property of a venom fraction against the HepG2 cell line (human hepatocellular carcinoma), with a mortality rate of 91.2% with an IC 50 value of 200 mg. As per the investigation of Almaaytah, Tarazi, Mhaidat, Al‐Balas, and Mukattash (2013), the toxin Mauriporin was isolated from the venom of Androctonus mauritanicus and exhibited tumoricidal characteristics against the PC‐3 (adenocarcinoma of human prostate), as well as LNCaP and DU 145 cell lines (carcinoma of prostate) with high mortality rates (Table 5).…”

“…B. martensii Karsch expressed caspase 3 and regulated Bcl‐2 negatively (Li et al, 2014). BmKn‐2 expressed caspase 3 and 9, and inhibited Bcl‐2 (Tong‐ngam et al, 2015). Fraction III presented negative regulation of Bcl‐2 and caspase 3 activity (Li et al, 2006).…”

Use of Animal Venom Peptides/Toxins in Cancer Therapeutics

“…Selectively targeting cancer tissue is one promising strategy. Similarly conjugation of toxins to platinum (IV) derivatives (Cisplatin), increase the cytotoxicity in cancer cells [185] (Table 3).…”