175
spectroscopy and nuclear magnetic resonance (NMR) confirmed the production of
the compound by these bacterial strains (Hill et al. 2007). Research studies to analyze the production in vitro from cultured strains of Vibrio sp. failed to give result.
Thus more research is yet to be done to finalize the bacterial symbiont that harbors
the synthesis pathway for production of KF. The mechanism of action of the compound remains to be elucidated.
Bryostatins are cyclic polyketides produced by the bacterial symbiont that lives
in association with the bryozoan Bugula neritina (Hale et al. 2002). All compounds
in the bryostatin family have macrolactone core complexes with three tetrahydropyran rings. The bryostatins can be differentiated among themselves based on the
substituents at positions C-7 and C-20 and depending on the presence of a γ-lactone
ring linked to C-19 and C-23 tetrahydropyran ring. The initial discovery of byrostatins was based on an anticancer-based bioassay fractionation. Among the bryostatins, bryostatin 1 is the most scientifically investigated and have been in clinical
trials. Bryostatin 1 is significant for the presence of a hydrophobic alkyl chain at
C-20. The compound associates with protein kinase C (PKC) at the regulatory
domain by specifically binding to the binding site of diacylglycerol (Nelson and
Alkon 2009). Short-time duration treatment by the compound leads to activation of
PKC, while long-time exposure induces prominent down regulation of PKC. In vitro
study in a range of cancer cell lines has shown to block proliferation leading to
apoptosis. Preclinical studies have revealed that bryostatin 1 has the property of
efficiently increasing the effects of chemotherapy. The compound has produced significant results when combined with standard chemotherapy thereby showing promise as a candidate for further study in cancer treatment (Kortmansky and Schwartz
2003). Research studies have shown that the compound can enhance the sensitivity
of cancer cells to cisplatin. Cisplatin is a major antitumor drug that is employed as
a chemotherapeutic agent in the treatment of various cancers, including cervical,
ovarian, and small-cell lung cancers (Alberts et al. 1991). Cisplatin therapy is
affected by tumor cell resistance, and PKC plays a significant role in cisplastin sensitivity. It is at this juncture where bryostatin can influence the action of PKC (Basu
and Lazo 1992).
Actinomycetes placed under the phylum actinobacteria are known for their filamentous nature and comes under the gram-positive bacteria (Ventura et al. 2007).
Actinomycetes follow a complex life cycle and remains well adapted across various
ecosystems. Nearly 23,000 bioactive secondary metabolites from microbes were
discovered by research investigations, and among these, 10,000 are sourced from
actinomycetes alone, accounting to 45% of all the secondary metabolites of microbial origin (Berdy 2005). Thus, this group forms a treasure house of bioactive compounds. The group has members that produce well-known anticancer drugs like
aclarubicin, doxorubicin, bleomycin, actinomycin D, pentostatin, mitomycins, and
many others (Olano et al. 2009; Newman and Cragg 2007). Polyketide-gene-derived
secondary metabolites with antitumor activity are well known within the
Streptomyces species.The polyketide gene family has a array of enzymes like ketoreductase, dehydratase and enoylreductase that works on the polyketide carbon
skeleton resulting in the end product secondary metabolite (Gokhale et al. 2007).
7 Anti Cancer Agents from Microbes
spectroscopy and nuclear magnetic resonance (NMR) confirmed the production of
the compound by these bacterial strains (Hill et al. 2007). Research studies to analyze the production in vitro from cultured strains of Vibrio sp. failed to give result.
Thus more research is yet to be done to finalize the bacterial symbiont that harbors
the synthesis pathway for production of KF. The mechanism of action of the compound remains to be elucidated.
Bryostatins are cyclic polyketides produced by the bacterial symbiont that lives
in association with the bryozoan Bugula neritina (Hale et al. 2002). All compounds
in the bryostatin family have macrolactone core complexes with three tetrahydropyran rings. The bryostatins can be differentiated among themselves based on the
substituents at positions C-7 and C-20 and depending on the presence of a γ-lactone
ring linked to C-19 and C-23 tetrahydropyran ring. The initial discovery of byrostatins was based on an anticancer-based bioassay fractionation. Among the bryostatins, bryostatin 1 is the most scientifically investigated and have been in clinical
trials. Bryostatin 1 is significant for the presence of a hydrophobic alkyl chain at
C-20. The compound associates with protein kinase C (PKC) at the regulatory
domain by specifically binding to the binding site of diacylglycerol (Nelson and
Alkon 2009). Short-time duration treatment by the compound leads to activation of
PKC, while long-time exposure induces prominent down regulation of PKC. In vitro
study in a range of cancer cell lines has shown to block proliferation leading to
apoptosis. Preclinical studies have revealed that bryostatin 1 has the property of
efficiently increasing the effects of chemotherapy. The compound has produced significant results when combined with standard chemotherapy thereby showing promise as a candidate for further study in cancer treatment (Kortmansky and Schwartz
2003). Research studies have shown that the compound can enhance the sensitivity
of cancer cells to cisplatin. Cisplatin is a major antitumor drug that is employed as
a chemotherapeutic agent in the treatment of various cancers, including cervical,
ovarian, and small-cell lung cancers (Alberts et al. 1991). Cisplatin therapy is
affected by tumor cell resistance, and PKC plays a significant role in cisplastin sensitivity. It is at this juncture where bryostatin can influence the action of PKC (Basu
and Lazo 1992).
Actinomycetes placed under the phylum actinobacteria are known for their filamentous nature and comes under the gram-positive bacteria (Ventura et al. 2007).
Actinomycetes follow a complex life cycle and remains well adapted across various
ecosystems. Nearly 23,000 bioactive secondary metabolites from microbes were
discovered by research investigations, and among these, 10,000 are sourced from
actinomycetes alone, accounting to 45% of all the secondary metabolites of microbial origin (Berdy 2005). Thus, this group forms a treasure house of bioactive compounds. The group has members that produce well-known anticancer drugs like
aclarubicin, doxorubicin, bleomycin, actinomycin D, pentostatin, mitomycins, and
many others (Olano et al. 2009; Newman and Cragg 2007). Polyketide-gene-derived
secondary metabolites with antitumor activity are well known within the
Streptomyces species.The polyketide gene family has a array of enzymes like ketoreductase, dehydratase and enoylreductase that works on the polyketide carbon
skeleton resulting in the end product secondary metabolite (Gokhale et al. 2007).
7 Anti Cancer Agents from Microbes