Prostate Cancer Joins Growing List of Cancers that Succumb to Cellceutix Corporation’s Potent Anti-Cancer Drug

Kevetrin Demonstrates Strong Anti-Tumor Activity in a Human Prostate Xenographt Model

BEVERLY, MA–(Marketwire – Oct 10, 2011) – Cellceutix Corporation (OTCQB: CTIX) (PINKSHEETS: CTIX) (“the Company”), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat unmet medical conditions, is pleased to report that as a result of its recent research, prostate cancer has been added to its Investigational New Drug (IND) application for Kevetrin™, the Company’s flagship compound in development as a new therapy for multi-drug resistant cancers. In addition to modifications for the prostate cancer research, the IND has been adjusted to include the clinical protocol for the hosting hospital.

The anti-tumor efficacy of Kevetrin™ was evaluated in the human LNCaP xenograft model. LNCaP are androgen-sensitive human prostate adenocarcinoma cells. Nude mice bearing established tumors were treated with 200 mg/kg Kevetrin intraperitoneally (IP) every other day for 3 weeks, while another group of mice were treated with the vehicle.

After only 1 week of dosing, the prostate tumors from mice treated with Kevetrin™ were significantly smaller (p < 0.01). The average tumor volume of Kevetrin™ treated mice was 25% of the control tumor volume after 1 week and further decreased to 14% of control after 3 weeks of dosing. Kevetrin™ significantly caused tumor growth delay (TGD) since control tumors reached 1000 mm3 in a median of 13 days, whereas, Kevetrin™ treated tumors required 25 days to reach that point (192% TGD). Importantly, this extended dosing regimen was very well tolerated based on no weight loss throughout the study.

The Company has prepared its regulatory submissions for the FDA. Presently the clinical section of the submission is undergoing a final review by the hosting hospital. Kevetrin is a drug that the Company believes will be effective against more than 50 percent of all cancers due to its reactivation of p53. The Company believes that no other anti-cancer drug has shown the ability to activate both transcription-dependent and transcription-independent pathways to promote apoptosis through p53 activation in tumor cells while being non-genotoxic. This expectation is based on the results of numerous tests in human cancer xenograft models. If these results are confirmed in the planned clinical studies, Kevetrin may fundamentally change the drug treatment for many types of cancers.

In order to better understand Kevetrin™ and its anti-tumor properties, the Company released the following excerpts from its regulatory application.

Anti-tumor activity in xenograft models. Kevetrin was tested for anti-tumor activity in human tumor xenograft models using 5 different carcinoma types: lung, breast, colon, prostate, squamous cell carcinomas, and in a leukemia tumor model… In addition, anti-tumor activity was demonstrated in multi-drug resistant tumor models… Kevetrin had greater anti-tumor activity compared to paclitaxel or cisplatin at approximately equitoxic doses despite being less cytotoxic, suggesting that Kevetrin may be targeting specific components of the signal transduction pathway, rather than being simply another cytotoxic agent.

Mechanism. Mechanism of action studies showed that Kevetrin strongly induced apoptosis in a human lung adenocarcinoma cell line (A549). Treatment of A549 cells with Kevetrin for 48 hours resulted in apoptosis induction that was characterized by activation of Caspase 3 and cleavage of PARP.

Reactivation of p53 in tumor cells has been recognized as a promising strategy for cancer treatment. The p53 tumor suppressor is a well characterized transcription factor controlling cell growth and apoptosis during times of cellular stress. Kevetrin activates both transcription-dependent and transcription-independent pathways to promote apoptosis through p53 activation in tumor cells.

Kevetrin activates both transcription-dependent and transcription-independent pathways to promote apoptosis. Kevetrin showed potent efficacy in various mutant and wild type tumor xenograft models, thus Kevetrin demonstrated effectiveness in a wide range of tumor types. Kevetrin enhanced the phosphorylation of MDM2 in a dose dependent manner. Phosphorylation of MDM2 alters the E3 ligase processivity. Stable monoubiquitinated form of p53 was induced by Kevetrin. MDM2 mediated monoubiquitination of p53 greatly promotes its mitochondrial translocation and thus its mitochondrial apoptosis. The induction of transcription-independent p53 induced apoptosis by Kevetrin has far reaching significance with tumor with mutant p53.

Inactivation of p53 by mutation occurs in ~50% of human cancers. Transcription mediated response of activated mutant p53 does not necessarily lead to apoptosis. Mutant p53 can act in the cytosol and mitochondria to promote apoptosis through a transcription-independent mechanism. Kevetrin can stabilize the transactivation-deficient mutant p53 and induce apoptosis.

Stable monoubiquitinated mutant p53 was induced by Kevetrin. This stable form of p53 accumulates in the cytoplasm and mitochondria and retains the ability to interact with BAK or BAX proteins in mitochondria to induce apoptosis.

Since Kevetrin activates both transcription-dependent and transcription-independent pathways to promote p53 activation, Kevetrin functions as a major inducer of apoptosis in many types of tumors independent of p53 mutation status. Activation of both modes of apoptosis by Kevetrin may not be mutually exclusive. Most likely, both modes of apoptosis induction cooperate and complement each other.

In summary, Kevetrin showed potent efficacy in several wild type and mutant p53 tumor xenografts e.g. A549, PC-3, MDA-MB-231, HT-29, NCI-H1975, HCT-15, and K-562. Kevetrin activated both wild type and mutant p53. Stable monoubiquitinated mutant p53 was induced by Kevetrin. This form of p53 has been shown to accumulate in the cytoplasm and mitochondria and retain the ability to interact with BAK or BAX proteins in mitochondria to induce apoptosis. Since Kevetrin activates both transcriptional-dependent and transcriptional-independent pathways to promote p53 activation, Kevetrin can function as a major inducer of apoptosis in many types of tumors independent of p53 mutation status. Activation of both modes of apoptosis by Kevetrin may not be mutually exclusive. Most likely, both modes of apoptosis induction cooperate and complement each other.