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Sources:The
seeds of Iris lactea Pall. var. chinensis (Fisch.) koidz.Family
Iridaceae.
Constituents:Containing
irisquinone (abbr.I), dihydroirisquinone, etc.
Actions:
(1) Anticancer actions: in vitro,
the IC50 for BEL-7420 cell line was 2.5ug/ -ml(48hrs) . The
IC50 for K562 and K562/AO2 (adriamycin tolerant cell line)
were 2.79 and 3.09¦Ìg/ml(72hrs) respectively.
So, It was effective against resistant adriamycin cell line.
The IC50 of I for all of the above cell lines were similar
with 5-FU.
In vivo, I 100~250mg/kg ig has
anticancer effect against lymphosarcoma, U14, LA795 and B16
solid tumor models, their inhibiting rates were 43.7%, 53.4%,
41.6%, and 53.1% respectively(P<0.01). 3~8mg/kg ip has
antican- cer effect against U14, S180 solid tumors , their
inhibiting rates were 55.5- % and 42%(P<0.01). 4~10mg/kp
ip has anticancer effect against EAC.H-
epA,S180 and B16 ascite tumor models, their prolongating rates
of life span were 835, 158%, 170% and 67%(P<0.01)respectively.
I combined
with chemotherapeutic agents, the anticancer action of chemotherapeutic
agents were enhanced significantly. Such as, I combined with
CTX, the anticancer efficiency of CTX against L615 leukemia
on mice, was enhanced significantly, the life span prolongating
rate group, to L615 mice was 43.5%, I group, was 25.8%, but,
in CTX combined with I group was 312.9%. So, the anticancer
effect of CTX was enhanced more than 7 times, from the eqution
of Q value calculation, the Q value= 5.39(note:Q value>1.15
was considered has enhancement action). In addition, the Icombined
with FT-207, the FT-207'S anticancer efficiency to S180 was
enhanced significantly,as well.
According to Zheng's report, I has reverse
action for adriamycin and harringtonine resistant L7712 leukemia.
The mechanisms of I for its anticancer
effects and chemosensitizing action:
1.I inhibited NDA synthesis of cancer
cells:
(2).I inhibited Topo II activity significantly,
its activity was similar with Vp16. (3) I inhibited the rejoining
and repair of single strands breaks of DNA induced by bleomycin
in L1210 cells. (2)Radiosensitizing effects: in vitro, I 0.1mmol
under hypoxic condition, its SER value was 1.68 for hela cell
line, similar with MISO, for CHO cell line SER was 1.59.
In vivo. I ig has ardiosensitizing effect
against MA737 and U14 tumors. For MA737 under hypoxic condition,
the SER was 1.33. In addition, under hypoxic condition, I
has radiosensitizing effect against human mucoaden- ointestinal
carcinoma on nude mouse.
The mechanisms of its radiosensitization:
(1)I was able to inhibit P388 cells respiration, so that it
makes the oxygen content of cells maintained in higher level.
(2) the content of GSH in hela cells was reduced by I both
in aerobic and hypoxic condition, especially in hypoxic condition,
GSH was reduced much more. (3) I could inhibit rejoining and
repair of DNA single strands breaks induced by radiation.
Indications:
I has been used for anticancer and ardiosensitization tretment
in cancers and leukemias.
(1) Anticancer:43 cases of acute leukemias
involving nlymphocytic ,granulo- cyte, mononucleocyte leukemias
have been treated by I capsules and I capsules combined with
chemotherapeutic agents, the results showed that 34 cases
were CR+PR, the effective rate was 79%, 38 cases treated with
I capsules alone, 29 cases were CR+PR, the effective rate
was 76%.
94 cases of solid tumors (lung, gastric,
liver and esophageal cancers) have been treated by I capsules
or I combined with chemotherapeutic agents, the results showed
that 59 cases were effective rate was 63% (among them 20 cases
combined with chemotherapy).
(2) Radiosensitization:Phase II clinical
trials. First clinical trial: the prospective randomized phase
II clinical trials on radiation combined with I capsules (test
group) and radiotherapy alone (control group) treatment for
lung cancer (218 cases), esophageal cancer(187 cases), head
and neck cancer (24 cases) and other cancers (29 cases), were
carried out in total 458 patients. The results showed that
the significant radiosensitizing effect of I capsules has
been proved, the CR rates of test group were significantly
higher than control group, especially in lung cancer group,
the long term survival rates in l, 3, 5year in test group
were significantly higher than that of control group, in addition,
the local cancer relapse rates in test group were significantly
reduced than the control group, as well.
Secodary phase II clinical trial: the
clinical trial was organized by two steps, in first step,
a double blind randomized clinical study was arranged ,383
cases of proven malignancies were divided into two groups,
the test group was treated with I capsules (140mg/m2/day)
orally combined with radiotherapy, the control group administered
same dose of placebo(maize flour) with radiotherapy. The results
showed that I capsules have significant radiosensitizing effect
for the primary tumors, but little effect for the metastatic
tumor. In second step, 573 cases with nasopharyngeal carcinoma(NPC),
head and neck cancers(HNC), non-small cell lung cancer (NSCLC)
and esophageal cancer were divided into two groups,in test
group, patients were given I capsules (140mg/m2/day) combined
with radiotherapy, the patients in control group were received
radiotherapy alone. For patients with HNC in test group, the
average PR and CR radiation dosage of primary tumor were 30.52+9.23
and 49.7+13.88 GY respectively and the CR rates of primary
tumor were 61.28%. All test groups were superior than that
of in control group, for the patients with NSCLC and esophageal
cancers, the response rates of half dosage and CR rates after
treatment were also superior in test group than that of control
group.
Phase III clinical trial: 2000 cases
of various kinds of cancers were randomized divided into two
groups one was treated with radiotherapy alone as control
group, the other group was treated with I capsules combined
with radiotherpy as test group. The administration method
of I capsule and dosage were same as in phase II clinical
trial. The results showed that I capsule has significant radiosensitizing
effect on lung, esophageal, nasopharyngeal, head and neck
cancers and so on. The adverse reactions, mainly were digestive
tract sied effects, but mild and tolerable, so generally could
completed the course of treatment.
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